Penetrating topical pain relief compositions and methods of use

ABSTRACT

Topical pain relief compositions include a cannabinoid, terpenoid, and skin penetration system that includes dimethyl sulfoxide (DMSO) and at least one compatibilizer. The composition may be in the form of an emulsion that contains water and at least one fatty component. The composition can be used to reduce or eliminate pain by direct topical application to an affected part or region of the body. A method of treating pain may include direct topical application of the composition to a joint, ligament, muscle, tendon, or disk. The composition penetrates through the skin to provide localized pain relief where applied and provides a quantity of cannabinoid in the region of the pain instead of distributing the cannabinoid systemically and/or to the brain or central nervous system. The composition may be applied by rubbing or massaging at the treatment site and/or by a bandage, patch or other barrier layer.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of U.S. application Ser. No.17/408,316, filed Aug. 20, 2021, which is a continuation-in-part ofInternational Patent Application No. PCT/US20/34984, filed May 28, 2020,which claims the benefit of U.S. Prov App No. 63/015,652, filed Apr. 26,2020, and U.S. Prov App No. 62/853,710, filed May 28, 2019, which areincorporated by reference in their entirety.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The invention is in the field of topical/transdermal compositions thatprovide localized pain relief, including highly penetrating compositionsthat contain one or more cannabinoids and a skin penetration system.

2. Relevant Technology

Managing pain is a basic necessity of life. Pain can strike people ofany age, gender and ethnicity without warning. Pain is a very strongmotivator. People will do almost anything to relieve pain, especiallyconstant pain that does not go away, including taking safe or dangerousmedications, many of which are highly addictive and can cause problemsworse than the underlying pain. The quest to relieve pain hascontributed to the opioid crisis, which claims tens of thousands oflives annually.

Pain comes in many forms. Some results from injury; some results fromdisease. Many types of pain are close enough to the surface that theycan be partially addressed by massage, liniments, and the like. Manypeople take daily doses of over-the-counter drugs such as non-steroidalanti-inflammatory drugs (NSAIDs) or acetaminophen for temporary reliefthinking they are safe because of their ubiquitous use. However,long-term use of pain killers causes organ damage, connective tissuedamage, ulcers, and tolerance. When these products stop working, manyturn to stronger drugs, like opioids, which are highly addictive,quickly cause dependence, and often cause death.

Recently, focus has turned to legalized forms of cannabis and extractedcannabinoids to relieve pain. Delivery methods range from smoking weed,inhaling vaporized oils, and consuming edibles. Some forms areintoxicating while others are not. Systemic delivery can relieve painbut may affect other aspects of the body unrelated to the pain.Delivering an analgesic systemically when pain is localized requiresorders of magnitude more analgesic than would otherwise be required ifdelivery were targeted.

While localized delivery of an analgesic is desirable, the skin acts asan almost impenetrable protective barrier that excludes most hydrophilicmolecules such as water and hydrophobic molecules such as vegetable oilsand cannabinoids. For this reason, topical cannabis products on themarket today, such as lotions, gels, creams, roller bottles, and solidpushup stick products, provide little or no actual pain relief.

Many topical products contain one or more counterirritants such asmenthol, methyl salicylate (oil of wintergreen), peppermint oil, andcamphor, which provide the common cold-hot sensation of traditionalliniments. While counterirritants provide the user with a sensation thatis interpreted to mean the product is “working”, they provide little orno therapeutic effect other than tricking the brain into focusing on thecold-hot sensation rather than the pain. Of the counterirritants, methylsalicylate may by metabolized to salicylic acid, a known NSAID. The factthat topical cannabis products typically contain one or morecounterirritants implies that the cannabinoids themselves have little orno effectiveness in treating pain. The most likely reason is lack ofadequate penetration through the skin where analgesia is needed.

Most topical CBD products list the amount of CBD in the container, whichis often required by law. It is also effective marketing and can demanda price corresponding to the stated quantity of CBD. However, if the CBDis unable to penetrate through skin but remains on the skin surface,applying such products is just “painting” the skin. If the CBD cannotpenetrate effectively through the skin, it cannot provide the advertisedor desired pain-relief (other than perhaps relieving superficial skinirritation). The amount of CBD in the product is often a gimmick thatbears no relationship to product effectiveness.

US 2016/0256411 to Aung-Din discloses a method of administering acannabinoid to one specific region, i.e., to the back of the neck regionat the hairline (BONATH), in order to deliver the cannabinoid directlyto the brain stem and/or trigeminal nerves to provide pain relief to adifferent part or region of the body. This is called topical regionalneuro-affective therapy (“TRNA therapy”). Aung-Din does not teach orsuggest that such composition is effective in treating localized pain(e.g., arms, hands, legs, feet, ankles, knees, back, shoulder, orbuttocks) by topical administration at the site of the pain for targetedlocal delivery and pain relief. By targeting interpretations of pain inthe brain, Aung-Din is a form of indirect, non-targeted pain relief.

US 2011/0052694 to Stinchcomb et al. discloses a microneedle injectionsystem designed to bypass the usual protective function of the epidermisto systemically deliver cannabinoid prodrugs. The microneedles formpores, holes or channels that provide a pathway for an otherwisenon-penetrating composition to pass through the skin. Stinchcomb '694reads like a pharmacopeia encyclopedia, listing literally thousands uponthousands of possible ingredients, including hundreds of unconnectedrange endpoints but no actual and meaningful ranges or amounts, and isdevoid of examples of actual compositions or how to make them. None ofthe “Examples” disclose actual compositions. Nor does Stinchcomb '694disclose that any composition was tested on a human to obtain useful andreliable feedback to determine if it would actually work to relievepain.

US 2009/0247619 to Stinchcomb et al. similarly disclosescannabinoid-containing compositions that were tested on laboratory ratsbut not humans. Stinchcomb '619 provides no evidence that the productwas effective to provide localized pain relief to a human. Rather,Stinchcomb '619 describes cutting and damage to tissue of laboratorytest animals to determine whether the composition promoted tissuehealing. Tissue wound healing, however, is not analogous to treatingchronic pain or even acute pain, particularly nagging pain that has noobvious or diagnosable cause or treatment.

US 2013/0274321 to Newland discloses the treatment of skin cysts andother conditions using a composition comprising a dimethyl sulfoxideextract of Cannabis sativa flower and bud leaves that contain at leastten weight percent of tetrahydrocannabolinic acid (THCA). The flower andleaves were heated for five minutes at a temperature of 160-193° C.,ground into a powder, mixed with dimethyl sulfoxide for 24 hours at roomtemperature, and filtered to yield the topical composition, which wasapplied topically or injected into a cyst. The amount of dimethylsulfoxide in the topical composition used in Examples 2-14 wasexcessively high, at least 98 wt % based on the amounts of cannabisplant powder and dimethyl sulfoxide used in Example 1 to make thecomposition, which can be dangerous and highly irritating to the skin.In Examples 15-18, the composition was diluted to 70% DMSO with anunspecified diluent and injected into a cyst or fistula.

In view of the foregoing, there remains a need for improved compositionsand methods that can provide localized topical delivery of cannabinoidsto treat localized pain, maximize pain-relieving properties, and reduceor minimize unwanted side effects.

SUMMARY

It has now been found that cannabinoids can be effectively deliveredtopically to provide fast, effective, and localized pain relief using anappropriate skin penetration system. The topical pain reliefcompositions have been found to be highly effective in providingpowerful localized analgesia to joints and muscles in various parts ofthe body, including arms, hands, fingers, legs, feet, ankles, knees,buttocks, back, shoulders, and neck.

In embodiments, a topical pain relief composition comprises acannabinoid component and a skin penetration system comprising dimethylsulfoxide (DMSO) and at least one compatibilizer. Example cannabinoidsinclude but are not limited to cannabidiol (CBD) and/ortetrahydrocannabinol (THC). Example compatibilizers include alcohols,polyols, thiols, carboxylic acids, carboxylates, polycarboxylates,esters, amides, ethers, sulfonates, phosphonates, and amines. Water canbe included to reduce skin irritation and possibly assist in penetrationof the DMSO and cannabinoid(s) through the skin.

The compositions can advantageously include a terpenoid component thatprovides additional analgesia in addition to the cannabinoid component.Example terpenoids include α-pinene, β-pinene, camphene, β-myrcene,humulene, α-bisabolol, β-caryophyllene, linalool, camphor, limonene,ocimene, α-phellandrene, 1,8-ceneole, γ-terpinene, terpineol, fenchol,phytol, nerolidol, geranyl acetate, sabinene, p-cymene, β-phellandrene,valencene, borneol, isoborneol, geraniol, δ-3-carene, and terpinolene.

When properly formulated and proportioned, the various componentsinteract together to maximize penetration and effectiveness of activepain-relieving components, while avoiding or minimizing irritation tothe skin. DMSO is effective in penetrating through skin and carryingcannabinoids and terpenoids with it to provide powerful localizedanalgesia. However, it was found that there is a limit to how much ofsuch compounds can effectively penetrate through the skin and provideeffective pain relief when topically applied. In other words, there isan optimal range of cannabinoids and terpenes that will provide the mosteffective pain relief. When the optimal range is exceeded, efficacy isdiminished. In other words, compositions containing greater amounts ofcombined cannabinoids and terpenoids can be less effective in relievingpain than compositions containing lesser amounts. This shows thateffective penetration of cannabinoids and terpenoids through the skin ismore important than their actual amounts in the formulation. It alsomeans that pain relief compositions according to the invention mayinclude less CBD than current compositions on the market, yet providesubstantially greater pain relief.

Unexpectedly, the disclosed compositions have been found to be effectivein treating, preventing, or reducing a wide variety of different typesof pain, as shown in the Examples below. Test results suggest asynergistic interaction between the DMSO, compatibilizer, andcannabinoid(s), and possibly also the terpenoid(s), that is able todeliver a level of fast and lasting pain relief that was heretofore notpossible using conventional topical analgesics.

In embodiments, the composition may comprise at least one fattycomponent, such as one or more fatty components selected from fattyacids, such as caproic acid, capric acid, caprylic acid, lauric acid,medium chain fatty acids (8 to 10 carbons), stearic acid, isostearicacid, octanoic acid, oleic acid, linoleic acid, or linolenic acid,esters of fatty acids, such as mono-, di- and/or triglycerides of fattyacids, preferably one or more of olive oil, sunflower seed oil, coconutoil, cocoa butter, jojoba oil, almond oil, pine needle oil, shea butter,argan oil, nigella sativa oil, beeswax, or flaxseed oil.

Although the fatty component would be expected to be inert and provideno pain relief, it was unexpectedly found that compositions that containDMSO, one or more cannabinoids, one or more terpenoids, one or morefatty components, water, and at least one compatibilizer, which can beproportioned to form an emulsion, appear to work particularly well inproviding pain relief, even better than solutions containing only DMSOand CBD and/or THC. Without being bound to any particular theory, it ispostulated that the combination of DMSO, water, fatty component, andcompatibilizer interacts with human skin to maximize penetration of thecannabinoid and optional terpenoid(s) through the skin. It is theorizedthat the combination causes localized softening of skin cells and/oropening of otherwise closed pores or pathways between or through thecells. It is further theorized that the fatty component forms a vaporbarrier that forces the more hydrophilic components to penetrate throughthe skin.

In some embodiments, a bandage, barrier or patch can be used incombination with the composition to protect it from being wiped off ortransferred before it has penetrated through the skin. A kit may includea container with the composition and one or more bandages or barriersfor use in applying and/or placement over the composition.

In some methods of treatment, it may be advantageous to re-apply thecomposition one or more times after the previous application haspenetrated through the skin to provide one more additional doses of painrelief. This can be particularly beneficial where the pain is locateddeeper below the skin and/or where the location of pain is difficult toaccess, e.g., where irritated tissue and/or nerves are blocked orimpeded by bony and/or sinewy tissue.

The disclosed compositions have been found to be especially useful intreating chronic pain, including chronic muscle pain, chronic tendonpain, chronic ligament pain, and chronic idiopathic pain with nospecific pathology or known cause, and in older (e.g., 50 or above) orinfirm persons, who have tried traditional pain remedies but with littleor no success.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the embodiments claimed.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Disclosed herein are topical pain relief compositions and methods fortopical and/or transdermal delivery of one or more cannabinoids andoptionally one or more terpenoids. A skin penetration system promoteseffective penetration of the cannabinoid(s) and optional terpenoid(s)through dermal and underlying tissue where applied. The pain reliefcompositions are highly effective in providing powerful localizedanalgesia to joints, ligaments, muscles, tendons, nerves, and disks invarious parts of the body, including arms, hands, fingers, legs, feet,ankles, knees, buttocks, back, shoulder, neck, and head.

In embodiments, a skin penetration system comprises dimethyl sulfoxide(DMSO) and at least one compatibilizer. Water and at least one fattycomponent have been found to further enhance effectiveness compared toDMSO alone. When properly formulated and proportioned, the variouscomponents synergistically interact together to maximize penetration andeffectiveness of active pain-relieving components while avoiding orminimizing irritation to the skin. The skin penetration system has beenfound to be highly effective in penetrating through skin and underlyingtissue and carrying cannabinoids and optional terpenoids with it toprovide powerful localized analgesia.

DMSO is miscible with water and other hydrophilic substances and candissolve several types of salts. However, DMSO is a relatively poorsolvent for hydrophobic resins and waxes contained in crude cannabisoils, which contain useful cannabinoids and terpenoids. Even though CBDand THC isolates are soluble in DMSO, it has been found, surprisinglyand unexpectedly, that solutions of DMSO and cannabinoid isolates ontheir own are quite ineffective in providing local pain relief whenapplied topically.

For this reason, compositions according to the invention advantageouslyinclude at least one compatibilizer, such as one or more amphiphilicorganic compounds, which help compatibilize and stabilize compositionscontaining DMSO, at least one cannabinoid, at least one terpenoid,water, and at least one fatty component. It is hypothesized thatcompatibilized and stabilized compositions, including emulsions andsuspensions where the components are substantially homogeneously mixedtogether, ensure close molecular proximity between individual DMSO,cannabinoid, and terpenoid molecules, while water, fatty component(s)and compatibilizer act to increase penetration and effectiveness of thepain relieving components of the composition.

In embodiments, the pain relief compositions comprise 8-80%, 11-75%, or15-70% DMSO by weight, such as greater than 11%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, or 60% DMSO by weight and less than 80%, 75%, or 70%DMSO by weight.

Example compatibilizers are amphophilic organic compound that include ahydrocarbon lipophilic portion and a polar hydrophilic portion with oneor more heteroatoms (O, N, S). Examples include alcohols, polyols,thiols, carboxylic acids, carboxylates, polycarboxylates, esters,amides, ketones, aldehydes, ethers, sulfonates, phosphonates, andamines.

Examples of compatibilizers that are more hydrophilic and lesshydrophobic include, but are not limited to, glycerin, amino acids,propylene glycol, 1,3-propanediol, 1,3-butanediol, sorbitol, xylitol,glucosides, sorbitan, polyethylene glycol, polysorbate, alcohols, lowerfatty acids, triethanolamine, carboxylic acids, polycarboxylic acids(e.g., partially neutralized polyacrylic acids), lower esters, ethylacetate, acetoacetic ester, 2-(2-ethoxyethoxy)ethanol, hydroxyacidesters, and ketones.

Examples of compatibilizers that are less hydrophilic and morehydrophobic include glycerides, isostearic acid, octanoic acid, oleicacid, oleyl alcohol, lauryl alcohol, ethyl oleate, isopropyl myristate,butyl stearate, methyl laurate, diisopropyl adipate, glycerylmonolaurate, tetrahydrofurfuryl alcohol, polyethylene glycol ether,polyethylene glycol, diethylene glycol monomethyl ether, diethyleneglycol monoethyl ether, alkylaryl ethers of polyethylene oxide,polyethylene oxide monomethyl ethers, polyethylene oxide dimethylethers, and N-alkylpyrrolidone. Such materials may constitute a fattycomponent depending on hydrophobicity.

It was discovered that DMSO, when used with a compatibilizer to form askin penetration system, is effective in carrying cannabinoids andterpenoids through the skin to provide localized pain relief.Cannabinoids and terpenoids have been found to be largely insoluble andform cloudy mixtures in solutions containing 70% DMSO and water,particularly waxy forms of extracted cannabinoids. DMSO is often used byitself in a 70% aqueous solution or gel to reduce or minimize skinirritation compared to more concentrated forms of DMSO. Adding acompatibilizer to replace or augment at least some of the water used todilute DMSO in topical formulations substantially improves theeffectiveness of the topical pain relief compositions compared to usingonly water. The compatibilizer can also provide skin soothing propertiesand act as an emollient.

It was further discovered that, while a skin penetration systemcontaining DSMO and at least one compatibilizer is highly effective infacilitating penetration of hydrophobic cannabinoids and terpenesthrough the skin to provide localized pain relief, there is a limit tohow much of such hydrophobic compounds can effectively penetrate throughthe skin when a dollop of pain relief composition is applied topicallyto skin. By adding different amounts of cannabinoids and terpenes to theskin penetration system and testing the different topical pain reliefcompositions, it was discovered that there is an optimal range ofcannabinoids and terpenes that will provide the most effective painrelief. When the optimal range was exceeded, the topical pain reliefcomposition appeared to be no more effective than compositionscontaining lower amounts of cannabinoids and terpenoids. In some cases,compositions that included greater amounts of cannabinoids andterpenoids were less effective in relieving pain than compositionscontaining lower amounts. This demonstrates that effective penetrationof the cannabinoids and terpenoids through the skin is far moreimportant than their actual amounts in the formulation. It also meansthat topical pain relief compositions according to the invention mayinclude less CBD and/or THC than current compositions on the market yetprovide substantially greater pain relief. This is demonstrated in theExamples below.

Example cannabinoids that can be useful in providing analgesia and otherbenefits include but are not limited to tetrahydrocannabinol (THC),tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolicacid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichchromene(CBC), tetrahydrocannabivarin (THCV), cannabicyclol (CBL),cannabidivarin (CBDV), cannabichromevarin (CBCV), and cannabigerovarin(CBGV). CBD is legal nationwide, highly effective, and a preferredcannabinoid. THC has several isomers. The main psychoactive component ofcannabis is delta-9-tetrahydrocannabinol. Another type isdelta-8-tetrahydrocannabinol. Yet another isdelta-11-tetrahydrocannabinol.

In some embodiments, the composition includes two or more cannabinoids,such as CBD and THC, particularly CBD and delta-8-tetrahydrocannabinolbut also CBD and delta-9-tetrahydrocannabinol or CBD anddelta-11-tetrahydrocannabinol. Evidence has shown that combining CBD andTHC provides faster and/or greater pain reduction than either CBD or THCalone.

In embodiments, the amount of the one or more cannabinoids can be in arange from about 0.003% to about 5%, about 0.004% to about 4%, about0.005% to about 3%, about 0.008% to about 2%, about 0.01% to about 1.5%,about 0.02% to about 1%, about 0.03% to about 0.7%, about 0.04% to about0.5%, about 0.05% to about 0.4%, about 0.06% to about 0.3%, or about0.07% to about 0.2%, by weight of the composition, or any range usingany two of the foregoing lower and upper endpoints. In otherembodiments, such as more highly penetrating liquid compositions, theone or more cannabinoids can be in a range from about 0.05-10%, or0.08-8%, or 0.1-6%, or 0.13-5%, or 0.15-4%, or 0.2-3%, or 0.3-2%, byweight of the composition, or any range using any two of the foregoinglower and upper endpoints.

In embodiments, the cannabinoid component can be water soluble or waterdispersible, such as liposomal droplets, aqueous nanosized cannabinoiddispersion, water-in-oil emulsion, or oil-in-water emulsion.

To provide an additional analgesic effect beyond that provided by theone or more cannabinoids, the topical pain relief compositionsadvantageously include one or more terpenoids. Example terpenoidsinclude α-pinene, β-pinene, camphene, β-myrcene, humulene, α-bisabolol,β-caryophyllene, linalool, camphor, limonene, ocimene, α-phellandrene,1,8-ceneole, eucalyptol, γ-terpinene, terpineol, fenchol, phytol,nerolidol, geranyl acetate, sabinene, p-cymene, β-phellandrene,valencene, borneol, isoborneol, geraniol, δ-3-carene, and terpinolene.The topical pain relief compositions include at least one, typically atleast two, preferably at least three, more preferably at least four, andeven more preferably at least five, of the foregoing terpenes.

In some embodiments, topical pain relief compositions may include, inapproximate or suggested order of prevalence: linalool, α-pinene,β-myrcene, β-caryophyllene, and humulene.

In other embodiments, topical pain relief compositions may include, inapproximate or suggested order of prevalence: β-myrcene, limonene,β-caryophyllene, humulene, linalool, β-pinene, α-pinene, α-bisabolol,terpineol, fenchol, phytol, nerolidol, geranyl acetate, camphene, andoptionally a proprietary blend of 7 additional terpenes.

In yet other embodiments, topical pain relief compositions may include,in approximate or suggested order of prevalence: linalool, β-myrcene,limonene, β-caryophyllene, α-pinene, humulene, β-pinene, α-bisabolol,terpineol, fenchol, phytol, nerolidol, geranyl acetate, camphene, andoptionally a proprietary blend of 7 additional terpenes.

The relative amounts and quantity of total terpenoids can be selected toprovide a desired pain relief profile. The amount of each terpenoid canbe expressed as a percentage of total terpenoids. The combined amount ofterpenoids can be expressed as a ratio of total terpenoids to totalcannabinoids. In some embodiments, the ratio (w/w) of total terpenoidsto total cannabinoids can be in a range of about 1:20 to about 10:1,about 1:15 to about 7:1, about 1:10 to about 5:1, about 1:9 to about3:1, about 1:7 to about 2:1, about 1:6 to about 1.5:1, about 1:5 toabout 1.2:1, or about 1:4 to about 1:1, by weight, or any range usingany two of the foregoing lower and upper endpoints.

The amount of the one or more terpenoids can be in a range from about0.002% to about 4%, about 0.003% to about 3%, about 0.005% to about2.5%, about 0.008% to about 2%, about 0.01% to about 1.5%, about 0.02%to about 1%, about 0.03% to about 0.7%, about 0.04% to about 0.5%, about0.05% to about 0.4%, about 0.06% to about 0.3%, or about 0.07% to about0.2%, by weight of the composition, or any range using any two of theforegoing lower and upper endpoints. In other embodiments,

The composition may include other components, such as essential oils,which typically include a blend of terpenoids, aspirin (acetyl salicylicacid), other NSAIDs or analgesics, methyl salicylate, menthol, arnicaoil, spikenard, peppermint oil, oil of wintergreen, or mixed pineterpenes, such as pure gum spirits of turpentine, which primarilycontains α-pinene and β-pinene, with lesser amounts of carene, camphene,dipentene, and terpinolene.

To provide effective penetration of the active pain-relievingcomponents, the topical pain relief pain compositions advantageouslycontain greater than 35%, 40%, 45%, 50%, 55%, or 60% by combined weightof DMSO and compatibilizer(s). In other embodiments, the compositionsadvantageously contain greater than 35%, 40%, 45%, 50%, 55%, or 60% bycombined weight of DMSO, compatibilizer(s), and water. In embodiments,the skin penetration system comprises DMSO and a compatibilizer in whichthe ratio of DSMO to compatibilizer is greater than 1:1 by weight, suchas a ratio of DMSO to compatibilizer(s) ranging from about 1:3 to about30:1, or about 1:2 to about 20:1, or about 1:1.5 to about 15:1, or about1:1 to about 12:1, or about 1.5:1 to about 10:1, or about 2:1 to about8:1, or about 2.5:1 to about 7:1, or about 3:1 to about 6:1, by weight.

In embodiments, the composition can be an emulsion or suspension inwhich the more hydrophilic compounds, including DMSO, hydrophiliccompatibilizer(s), and water, form a continuous phase and the morehydrophobic compounds, including cannabinoids, terpenoids, andhydrophobic compounds, are dispersed as a discontinuous phase. It isespecially beneficial for cannabinoids and terpenoids to be dispersed astiny droplets, preferably nano-sized droplets between about 5-1,000 nm,such as about 10-600 nm, or about 15-400 nm, or about 20-200 nm, insize.

To maintain a stable emulsion or suspension in which the cannabinoidsand terpenoids remain as tiny highly dispersed droplets, the compositionmay include a gel-forming agent, examples of which include carbomer,polyethylene oxides, poloxamers, vegetable gums, gelatin, pectin,alginates, agar, polysaccharides, proteins, and the like. It isbeneficial to limit the amount of such components to no more than about5%, 4%, 3%, 2%, 1%, 0.5%, or 0.25% by weight of the composition. Thegel-forming agent is typically amphiphilic and may augment thecompatibilization effects of other compatibilizers. However, because oftheir generally large molecular structures, gel-forming agents willtypically not penetrate beyond the outer epidermal layer.

In some embodiments, the composition can include at least one fattycomponent, such as one or more fatty components selected from fattyacids, such as caproic acid, capric acid, caprylic acid, lauric acid,medium chain fatty acids (6-12 or 8-10 carbons), stearic acid,isostearic acid, octanoic acid, oleic acid, linoleic acid, or linolenicacid, esters of fatty acids, such as mono-, di- and/or triglycerides offatty acids, preferably one or more of olive oil, sunflower seed oil,coconut oil, cocoa butter, jojoba oil, almond oil, pine needle oil, sheabutter, argan oil, nigella sativa oil, beeswax, and flaxseed oil, andα-tocopheryl acetate. Amphiphilic fatty components, such as lower fattyacids and esters, may function as a compatibilizer.

Although the fatty component would be expected to be inert and provideno pain relief, it was unexpectedly found that compositions that containDMSO, one or more cannabinoids, one or more terpenoids, one or morefatty components, water, and at least one compatibilizer, which can beproportioned to form an emulsion, appear to work particularly well inproviding pain relief, even better than solutions containing only DMSOand CBD and/or THC. Without being bound to any particular theory, it ispostulated that the combination of DMSO, water, fatty component, andcompatibilizer interacts with human skin to maximize penetration of thecannabinoid and optional terpenoid(s) through the skin. It is theorizedthat the combination causes localized softening of skin cells and/oropening of otherwise closed pores or pathways between or through thecells. It is further theorized that the fatty component forms a vaporbarrier that forces the more hydrophilic components to penetrate throughthe skin.

In some embodiments, a bandage, barrier or patch can be used incombination with the topical pain relief composition to protect it frombeing wiped off or transferred before it has penetrated through theskin. A kit may include a container with the composition and one or morebandages or barriers for use in applying and/or placement over thecomposition. A kit of one or more patches loaded with the compositionmay be provided.

In some methods of treatment, it may be advantageous to re-apply thecomposition one or more times after the previous application haspenetrated through the skin to provide one more additional doses of painrelief. This can be particularly beneficial where the pain is locateddeeper below the skin and/or where the location of pain is difficult toaccess, e.g., where irritated tissue and/or nerves are blocked orimpeded by bony and/or sinewy tissue.

The composition can have a form selected from cream, lotion, gel,suspension, ointment, high-viscosity liquid, medium viscosity liquid, orlow viscosity liquid. The composition is advantageously in the form of acream, gel, or liquid to enhance the ability to penetrate through theskin to provide local pain relief. In general, the ability of thecompositions to quickly and effectively penetrate through the skingreatly enhances efficacy and reduces the amount of cannabinoids andterpenoids required to provide pain relief, both therapeutic andprophylactic.

The amount of CBD or other cannabinoid required to provide local painrelief can be about 5 mg or less, 3 mg or less, 2 mg or less, 1.5 mg orless, 1 mg or less, 0.75 mg or less, or 0.5 mg or less. By comparison,the amount of CBD or other cannabinoid, when orally administered, thatis required to provide a therapeutic effect is reportedly 10 mg or more,15 mg or more, 20 mg or more, or 25 mg or more. Topical compositionsthat cannot penetrate through the epidermis may provide the same or morecannabinoids and yet provide little or no pain relief. Therefore, theimportant thing is the bioavailable dose, not dosage per se.

Similarly, the amount of total terpenoids required to provide local painrelief can be about 5 mg or less, 3 mg or less, 2 mg or less, 1.5 mg orless, 1 mg or less, 0.75 mg or less, 0.5 mg or less, 0.3 mg or less, or0.1 mg or less.

The pain relief compositions are advantageously not provided as a thickwaxy composition as is common with many commercially available topicalCBD formulations, which appear to remain as a coating on the skin whereapplied.

The composition can be provided as a muscle rub, massage oil, spray, orroll-on.

Pain relief compositions disclosed herein have been found to beeffective in providing rapid and lasting relief for a wide range ofmuscular, joint and other pain conditions including, but not limited to,neck pain, shoulder pain, muscular pain, back pain, joint pain, kneepain, hamstring pain, arm pain, tennis elbow, bunions, ankle pain, footpain, hand pain, finger joint pain, wrist pain, pinched nerves,degenerated disc, headaches, plantar fasciitis, and pain resulting fromneuromuscular conditions, such as multiple sclerosis, Parkinson'sdisease, and cancer. The compositions have also been found to beeffective to provide prophylactic relief, such as pre-workout or priorto intense activity to prevent or reduce subsequent pain from happeningthat would normally occur. Examples include prior to lifting weights,hiking, biking, running, tennis, golf, playing drums, guitar or othermusical instrument, typing at a computer, and driving a car.

EXAMPLES

The following Examples include descriptions of comparative CBD- andTHC-containing compositions (i.e., commercial formulations) that werefound to provide little or no pain relief, and penetrating topical painrelief compositions of the disclosed invention, which were found to besubstantially more effective in providing pain relief than thecomparative compositions, typically at the same or lesser percentageand/or dosage of cannabinoid.

Comparative Example A

A CBD balm was provided in the form of a waxy pushup stick similar to acommon deodorant stick, with a solid composition that is advanced usinga twist knob within an oval plastic container and mating shell top. Thelabel states the CBD balm is “extra strength advanced heated relief”containing 200 mg CBD in 2.5 oz (75 g) of total balm (0.267% CBD w/w).The ingredients (not in order of prevalence) are: “Cannabidiol (CBD),Menthol Crystals (DL-Menthol), Camphor Oil (Cinnamomum Camphora), ArnicaMontana Extract (Helianthus Annus), Peppermint Oil (Mentha Piperita),Beeswax (Cera Alba), Coconut Oil (Cocos Nucifera), Grapeseed Oil (VitisVinfera), Eucalyptus Oil (Eucalyptus Globulus Leaf Oil), Vitamin E(Tocopherol), Caffeine Oil, Proprietary Scent.”

A 58-year-old man suffering from constant neck and shoulder pain forseveral weeks purchased Comparative Example A from an alternativemedicine clinic with the goal of obtaining pain relief. The subjectapplied the product to the affected area and immediately felt a coolingsensation and noticed the smell of menthol and other aromatics in thebalm. However, the man experienced no pain relief even though thecooling sensation and smell persisted for hours.

A male body builder in his late 30s suffering from inner tendonitis atthe elbow where the bicep muscle attaches to the ulna applied the CBDbalm and experienced no pain relief.

A 54-year-old man who is an ultra-marathon runner and avid hiker hadbeen suffering from sharp bunion pains in both feet. The subject appliedthe CBD balm to sore areas in the foot and experienced no pain relief.

A 30-year-old professional skier applied the CBD balm to sore musclesand joints and experienced no pain relief.

It is hypothesized that the CBD was unable to provide pain reliefbecause it could not penetrate through the skin but remains on thesurface with other oily components. In comparison, pain reliefcompositions of the disclosed invention (e.g., Examples 1-10) containingless than half the concentration of CBD (about 66.7 mg CBD in 2 oz (60g) of composition, or 0.11% CBD) were highly effective in providing painrelief within minutes or seconds of application. In one case, a painrelief composition similar to Example 2 below was applied to theaffected area over the top of the previously applied CBD balm ofComparative Example A and provided significant pain relief. Thisdemonstrated that penetration of the inventive composition through theskin was not impeded by the previously applied CBD balm and was thecritical factor affecting relief.

Comparative Example B

A CBD balm was provided in the form of a lotion in a pump bottle thatreportedly contains 250 mg “full CBD” in 1 ounce (0.845% w/v) andprovides “8 mg per pump”. The label instructs the user to “applydirectly to skin, muscles & joints”. The listed ingredients are “250 mgof cannabidiol (CBD) from Cannabis sativa L (whole hemp plant” . . . ,All-Natural Aloe Leaf Juice, Meadow-Foam Seed Oil, Camphor Bark OilMenthol Crystals, Capsicum Fruit Ole-Resin, Roman and German ChamomileFlower, Cinnamon Leaf Oil, Citronella Oil, Eucalyptus Leaf Oil,Helichrysum Flower Oil, Ginger Root Oil, Pink Grapefruit Peel Oil,Juniper Berry Oil, Lemon-Grass Oil, Peppermint Oil, Pine Needle Oil,Ravensara Oil, Rosemary Leaf Oil, Spearmint Oil, Wild Oregano Oil,Glycerin, Tetrasodium Glutamate Di-acetate, Alcohol, Phenoxyethanol,Carbomer Triethanolamine, Which Hazel Water.”

The 58-year-old man who suffered from neck and shoulder pain purchasedComparative Example B from a local pharmacy, which said it won awardsfor best topical CBD, applied it to a sore joint, felt a coolingsensation, and noticed the smell of menthol, mint and other aromatics inthe balm. However, the subject experienced little to no pain reliefalthough the product purportedly contained about three times theconcentration of CBD compared to the composition of Comparative ExampleA.

The 54-year-old ultramarathon runner applied the CBD balm to sore areasin the foot and experienced no pain relief.

It is hypothesized that there is minimal penetration of the CBDcomponent through the skin. In comparison, pain relief compositions ofthe disclosed invention (e.g., Examples 1-10) containing aboutone-seventh the quantity of CBD (about 66.7 mg CBD in 2 oz (60 g) ofcomposition) (0.11% CBD) were highly effective in providing pain reliefwithin minutes or seconds of application.

Comparative Example C

Synergy Relief CBD & THC Infused Balm sold by Planet 13, Las Vegas,Nev., reportedly contains 50 mg CBD and 50 mg THC in 1.7 oz (50 g) ofthe balm (0.1% CBD w/w and 0.1% THC w/w).

The label for the Synergy Relief product used in this example listed thefollowing ingredients (presumably in order of prevalence): olive oil(extra virgin), lobelia olive oil, beeswax, castor oil, CBD isolate,cocoa butter, essential oil blend (proprietary), and THC. The totalcannabinoid analysis in 100 mg of cannabinoids: 45.939 mg THC, 49.824 mgCBD, 0.0 mg CBG, 4.191 mg THCV, and 0.0 mg THCVa. Total terpenes in theproduct were: eucalyptol 13.546 mg, camphene 9.220 mg, alpha-pinene24.648 mg, and linalool 11.024 mg.) The weight ratio of total terpenoids(58.438 mg) to total cannabinoids (99.954 mg) was therefore 0.585:1, ora little more than 1:2.

A more recent label for a different lot of Synergy Relief CBD & THCInfused Balm listed the following ingredients (presumably in order ofprevalence): Infused Olive Fruit Oil (Olea Europaea Fruit Oil),Isopropyl Alcohol, Lobelia Inflata Seed Extract, Cara Alba (Beeswax),Ricinus Communis (Castor) Seed Oil, Theabroma Cacao (Cocoa) Seed Butter,Rosemarinus Officinalis (Rosemary) Oil, THC Oil, CBD Oil, LavadulaOfficinalis (Lavender) Flower Oil, Cedrus Deodara (Cedarwood) Oil, PinusSylvestris (Pine) Needle Oil.”

The 58-year-old man suffering from neck and shoulder pain applied theCBD & THC Infused Balm several times to the affected area butexperienced no noticeable pain relief. The composition of ComparativeExample C was modified as disclosed herein by mixing it with a skinpenetration system that included DMSO. The 58-year-old man applied themodified composition to the neck and shoulder and, rather surprisinglyand unexpectedly, obtained fast, effective, and long-lasting painrelief.

The 54-year-old ultramarathon runner applied the CBD & THC Infused Balmto sore areas in the foot and experienced no pain relief. The54-year-old man applied the modified composition (according to theinvention) to the same sore areas of the foot and obtained fast,effective, and long-lasting pain relief.

Comparative Example D

A commercially available THC-infused muscle relief lotion comprises112.5 mg CBD in 4 oz (118 mL) of the lotion (0.1% THC w/v). The labellisted the following ingredients (presumably in order of prevalence):infused olive fruit oil (Olea Europa Fruit Oil), isopropyl alcohol,lobelia inflata seed extract, aloe barbadensis leaf juice, water, Cocosnucifera (coconut) fruit oil, emulsifying wax, mixed naturaltocopherols, Theobroma cacao (cocoa) seed butter, Rosmarinus officinalis(rosemary) oil, Lavandula officinalis (lavender) flower oil, cedrusdeodara (cedarwood) oil, Pinus sylvestris (pine) needle oil, boswelliaserrata (frankincense) gum oil, and cannabis oil. The terpene analysisfor the product was: alpha-pinene 3.432 mg/g, linalool 2.013 mg/g, andlimonene 1.832 mg/g.

A 59-year-old man suffering from various muscle and joint pains appliedComparative Example D to affected areas but experienced little or nopain relief.

Comparative Example E

A DMSO cream with aloe vera (rose scented) contained 70% DMSO, 30% aloevera in a cream base was purchased online. The 58-year-old man sufferingfrom constant neck and shoulder pain for several weeks first applied theDMSO cream to the affected area and possibly obtained some pain relief,but only briefly. However, the rose smell was strong and made the manfeel nauseous and self-conscious. The pain returned as usual.

Comparative Example F

A solution containing primarily DMSO and CBD was made and applied by the58-year-old man to various places where the inventive composition wasfound to provide effective pain relief. It was believed that removingfatty components and other inert materials that are not known to providepain relief would make the composition more effective. In fact, thecomposition was largely ineffective, providing little to no noticeablepain relief. This was surprising and unexpected and appears to point tothe importance of including the compatibilizer, water, and one or morefatty components, in addition to the DMSO, cannabinoid(s), and optionalterpenes.

Comparative Example G

A solution containing primarily DMSO and a blend of terpenes containing,among other things, linalool, α-pinene, β-myrcene, β-caryophyllene, andhumulene, was made and applied by the 58-year-old man to various placeswhere the inventive composition was found to provide effective painrelief. There are reports of terpenes contributing some or most of thepain relief offered by cannabis extracts. The composition wasineffective, providing no noticeable pain relief. While terpenes canhelp provide an entourage effect when combined with one or morecannabinoids, they were ineffective by themselves when applied usingDMSO as the carrier.

Example 1

The Synergy Relief CBD & THC Infused Balm of Comparative Example C wasmixed with pharmaceutical grade (99.995%) DMSO at a ratio of about 1:1.The resulting topical composition was a thin runny suspension thatseparated into phases and required agitation before use. Addition ofabout 10% of vegetable glycerin helped to stabilize the compositionsomewhat. The composition contained about 0.05% w/v CBD and about 0.05%w/v THC, or about 0.1% total cannabinoids and about 0.06% totalterpenes.

The 58-year-old man suffering from constant neck and shoulder pain forseveral weeks, who had previously tried Comparative Examples A, C and E,applied Example 1 to the neck and shoulder area and experienced nearlytotal pain relief within about 5 minutes. The pain relief lasted forabout 12 hours. The subject re-applied the composition 2-3 times per dayfor 3-4 days, has obtained essentially permanent pain relief, and hasbeen able to manage and eliminate the pain if it arises. Whatever paindoes arise from time to time is substantially less than the pain priorto first using Example 1 but after multiple applications of ComparativeExamples A, C and E to the affected area.

The 54-year-old ultra-marathon runner applied the composition of Example1 to both feet and noticed a pain reduction of about 50-70% in 10-20minutes. The man re-applied the composition before going to bed. Thenext morning the man awoke with virtually no pain in either foot.

Example 2

A commercially available CBD hand and body lotion (CBD SFV/KlashnikovaTerpenes—Migraine & Pain) sold by Koodegras (Sandy, Utah), whichreportedly contains 400 mg CBD in 6 fluid ounces of lotion (0.225% w/v)in a glass jar, was mixed with DMSO and glycerin to form a topicalcomposition in the following amounts:

CBD Lotion 40 grams DMSO (99.995%) 30 milliliters Glycerin 10milliliters

The label for the CBD hand and body lotion listed the followingingredients (presumably in order of prevalence): “Purified water,Capric/Caprylic Triglycerides, (Sunflower) Seed Oil, Hemp CBD Oil withTerpenes, Moroccan Organic Argan Oil, Emulsifying Wax, GlycerylMonostearate, Simmondsia (jojoba) oil, Butyrospermum Parkii (SheaButter), Stearic Acid, Cetyl Alcohol, Glyceryl Distearate, andCarbomer.” The CBD hand and body lotion inherently contained thefollowing terpenes/terpenoids (in approximate order of prevalence):linalool, myrcene, limonene, β-caryophyllene, α-pinene, humulene,β-pinene, α-bisabolol, terpineol, fenchol, phytol, nerolidol, geranicacid, camphene, and a proprietary blend of 7 additional terpenes. Theratio of CBD to terpenes was about 3 parts CBD to about 1-2 parts totalterpenoids by weight.

The resulting topical composition of Example 2 contained about 0.11% CBDw/v, with a ratio of about 3 parts CBD to about 1-2 parts totalterpenoids by weight, and was a thin cream that remained as a stableemulsion.

The 58-year-old man suffering from constant neck and shoulder pain forabout one month, who had previously applied Example 1 to the neck andshoulder, applied Example 2 to the neck and shoulder area after some ofthe pain returned and experienced nearly total pain relief in 10-20minutes. The pain relief lasted about 12 hours. The composition wasre-applied for the next few days with similar results. This product wasused for several weeks and provided the subject with virtually total andlasting pain relief.

The 54-year-old ultra-marathon runner applied the composition of Example2 to both feet and obtained fast, effective and long-lasting painrelief. The man has been using this composition to scale numerousmountains and run ultramarathons ever since and attributes his abilityto effectively manage the pain associated with these hard physicalactivities to Example 2 and similar compositions.

The male body builder who applied Comparative Example A applied thecomposition of Example 2 to the affected area and obtained relief, evenafter applying this composition over the top of previously appliedComparative Example A. The man had been scheduled for surgery to repairthe arm tendon, but after 4 months of using Example 2 and similarcompositions of the invention, and performing physical therapy, he andhis surgeon cancelled the surgery.

Example 3

A commercially available CBD black seed salve (Sacred Herbal MedicinalRemedies) sold by Koodegras, which reportedly contains 900 mg CBD in 6fluid ounces (0.5% CBD w/v), was mixed with DMSO (99.995%) and glycerinto form a topical composition in the following amounts:

CBD Salve 40 grams DMSO 30 milliliters Glycerin 10 milliliters

The label for the CBD black seed salve listed the following ingredients(presumably in order of prevalence): Organic Olive Oil, Black Seed(Cumin) Oil, Coconut Oil, Jojoba Oil, Sweet Almond Oil, Argan Oil,Nigella Sativa Oil, Shea Butter, Beeswax, Hemp CBD Oil, SkullcapCharcoal, Arnica, Passionflower, Vitamin E, Tocopherol, Camphor, WhiteWillow Oil, Rosemary, Turmeric Lavender, Frankincense, Capsicum Annum,And Essential Oils And Herbal Blends (Proprietary).

The resulting topical composition contained about 0.25% CBD w/v, with aratio of about 3 parts CBD to about 1-2 parts total terpenoids by weightand was a thick emulsion that appeared to be relatively stableovernight.

The 58-year-old man suffering from nagging pain in the left shoulder andneck area for about one month applied the topical composition to thearea when some of the pain returned and experienced substantial painrelief. The composition left a heavier oily skin residue compared to thecomposition of Example 2 and did not appear to penetrate as completely.

A 48-year-old man suffering from arm pain that impaired his golf swingapplied the composition and obtained almost total relief. The only sideeffect was a funny taste in his mouth, which was likely from the blackseed sativa components. He shared the composition with a golfer friendwho had intense shoulder pain, which had prevented his natural swing,and he was able to resume golfing with his normal swing.

Example 4

The composition of Example 3 was mixed with an additional 40 millilitersof DMSO (99.995%) and 5 milliliters of glycerin to form a thinner, runnymaterial, which separated into layers over time (about 0.167% CBD w/v).The composition was agitated before application, was more penetrating,left less residue than the composition of Example 3, and provided aboutthe same pain relief as Examples 1 and 2.

Example 5

A commercially available CBD salve (No. 9 Time-Released Quick ReliefSalve) sold by Koodegras, which reportedly contains 200 mg CBD in 2fluid ounces (0.338% CBD), was mixed with DMSO (99.995%) at a ratio of1:1 to form a topical composition.

The label for the CBD No. 9 salve listed the following ingredients(presumably in order of prevalence): Argan Oil, Black Seed Oil, OliveOil, Organic Beeswax, Proprietary Asian Herbal Mix, Vitamin E Oil, MixedTocopherols, Anhydrous Hemp Oil, Time Release CBD Oil, ProprietaryEssential Oil Blend, Melaleuca Oil, Eucalyptus Oil, Cayenne Oil, AndBeta-Caryophyllene.

The resulting topical composition contained about 0.169% CBD w/v) with aratio of about 3 parts CBD to about 1-2 parts total terpenoids by weightand was a thick emulsion that was relatively stable and requiredoccasional agitation to resuspend. Addition of vegetable glycerin helpedstabilize the composition, reduce odor of the DMSO, and yielded acomposition containing about 0.15% CBD w/v and associated terpenoids.

A person suffering from pain applied the topical composition to the areawhere pain was experienced and obtained nearly total pain relief thatlasted about 12-24 hours. The composition was re-applied as needed andprovided consistent pain relief.

Example 6

A commercially available water-borne nanosized CBD dispersion (AngstromPlexll phytocannabinoid complex) sold by Koodegras, which reportedlycontains 250 mg CBD in 10 milliliters (2.5% CBD w/v), was mixed withDMSO (99.995%) at a ratio of 1:1 to form a topical compositioncontaining about 1.25% CBD.

The label for the CBD Angstrom Plexll dispersion listed the followingingredients (presumably in order of prevalence): Purified Water, OliveOil, Sunflower Lecithin, Anhydrous Hemp Oil, Potassium Sorbate, VitaminE, And Citric Acid.

The resulting topical composition was a thin non-viscous fluidsuspension that was relatively stable but may require occasionalagitation to resuspend. Addition of vegetable glycerin appears to havestabilized the suspension and reduced the odor of the DMSO.

A person suffering from pain applied the topical composition to the areawhere pain was experienced and obtained nearly total pain relief thatlasted about 12-24 hours. The composition was re-applied as needed andprovided consistent pain relief.

7Examples 7A-7R

Examples 7A-7R were made by mixing Base Composition A as a source of CBDand terpenoids with other components to yield topical pain reliefcompositions. Base Composition A was an emulsion manufactured for theinventor in 1-gallon amounts and contained a quantity of hemp CBD oilthat provided 10,000 mg of CBD per gallon (0.264% CBD w/v) andterpenoids in a ratio of about 3 parts CBD to about 1-2 parts totalterpenoids by weight.

Base Composition A

Base Composition A contained the following in order of prevalence:

  Purified water Capric/Caprylic Triglycerides Sunflower Seed Oil HempCBD Oil with Terpenes Moroccan Organic Argan Oil Emulsifying WaxGlyceryl Monostearate Simmondsia (jojoba) oil Butyrospermum Parkii (SheaButter) Stearic Acid Cetyl Alcohol Glyceryl Distearate Carbomer.

The ratio of CBD to total terpenes was about 3 parts CBD to about 1-2parts total terpenoids. The relative amount of each terpenoid as apercentage of total terpenoids was approximately:

Linalool   75% α-Pinene   11% β-Myrcene 10.5% β-Caryophyllene   2%Humulene  1.5%

Base Composition A (“A”) was mixed with components in the amounts inTables 1 and 2 to yield the compositions of Examples 7A-7P.

TABLE A Example Component 7A 7B 7C 7D 7E 7F 7G 7H 7I A 25 g 40 g 250 g80 g 160 g 300 g 200 g 300 g 500 g DMSO 20 ml 40 ml 250 ml 80 ml 160 ml300 ml 200 ml 300 ml 500 ml Glycerin 1 g 10 ml 62.5 ml 20 ml 40 ml 75 ml50 ml 75 ml 125 ml Gel (70/30 2 g 10 g 60 g 20 g 40 g 70 g 70 g 70 g 100g DMSO:Water) *White Camphor 0.5 ml 0.5 ml 2 ml 1.25 ml 1.5 ml 1.5 ml 2ml 3 ml 6 ml Oil of 2 ml 2 ml 3 ml 6 ml Wintergreen Arnica 3 ml 2 ml 2ml 4 ml Mixed pinenes 6 ml *White Camphor: α-Thujene (0.33%),α-Pinene(2.3%), camphene (0.99%), sabinene + β-pinene (13%),6-methyl-5-heptene-2-one (0.11%), β-Myrcene (9.24%), δ-2-carene (0.1%),α-phellandrene (3.63%), δ-3-carene (0.23%), α-terpinene (5.01%),p-cymene (9%), 1,8-cineole + β-phellandrene + limonene (55.17%),γ-terpinene (0.06%), and α-terpinolene (0.03%)

TABLE B Example Component 7J 7K 7L 7M 7N 7O 7P 7Q 7R A 600 g 800 g 16070 g 600 g 600 g 600 g 200 g 300 g DMSO 600 ml 800 ml 160 ml 80 ml 600ml 600 ml 600 ml 200 ml 300 ml Glycerin 150 ml 200 ml 40 ml 20 ml 120 ml150 ml 150 ml 25 ml Gel (70/30 25 g 40 g 21 g 100 g 70 g 70 g 25 g 30 gDMSO:Water) Gel (85/15 water 125 g 200 g to MSM) *White Camphor 7 ml 9ml 1.5 ml 1.25 ml 7 ml 0.5 ml 1 ml 3 ml Oil of 7 ml 9 ml 2 ml 0.5 mlWintergreen Arnica 4 ml 5 ml 0.5 ml Mixed pinenes 7 ml 10 ml 2 ml 1 mlMenthol 2 g 1 g THC:CBD Balm 10 g Spikenard 0.6 ml 0.3 ml Essential Oil{circumflex over ( )}Klash Terpenes 0.5 ml 0.5 ml Linalool 3.85 ml 4 ml1 ml α-Pinene 0.5 ml 0.75 ml β-myrcene 0.5 ml 0.75 ml 0.5 ml humulene0.1 ml 0.2 ml 0.15 ml β-caryophyllene 0.1 ml 0.2 ml 0.5 ml *WhiteCamphor: α-Thujene (0.33%), α-Pinene(2.3%), camphene (0.99%), sabinene +β-pinene (13%), 6-methyl-5-heptene-2-one (0.11%), β-Myrcene (9.24%),δ-2-carene (0.1%), α-phellandrene (3.63%), δ-3-carene (0.23%),α-terpinene (5.01%), p-cymene (9%), 1,8-cineole + β-phellandrene +limonene (55.17%), γ-terpinene (0.06%), and α-terpinolene (0.03%){circumflex over ( )}Klash Terpenes: Linalool(75%), α-Pinene (11%),β-Myrcene (10.5%), β-Caryophyllene (2%), Humulene (1.5%)

The resulting compositions of these examples are stable lotions thatprovided fast, effective and long-lasting pain relief when topicallyapplied by several individuals, such as those referenced in Examples11A-11BA.

Example 8

Example 8 was made by mixing Base Composition B as a source of CBD andterpenoids with other components to yield a topical pain reliefcomposition. Base Composition B was an emulsion manufactured for theinventor in 1-gallon amounts and contained a quantity of hemp CBD oilthat provided 10,000 mg of CBD per gallon (0.264% CBD w/v) andterpenoids in a ratio of about 3 parts CBD to about 1-2 parts totalterpenoids by weight.

Base Composition B

Base Composition B contained the following in order of prevalence:

Purified water   Capric/Caprylic Triglycerides Sunflower Seed Oil HempCBD Oil with Terpenes Moroccan Organic Argan Oil Emulsifying WaxGlyceryl Monostearate Simmondsia (jojoba) oil Butyrospermum Parkii (SheaButter) Stearic Acid Cetyl Alcohol Glyceryl Distearate Carbomer.

The ratio of CBD to total terpenes was about 3 parts CBD to about 1-2parts total terpenoids. The relative amount of each terpenoid as apercentage of total terpenoids was approximately:

β-Myrcene  30% Limonene  25% β-Caryophyllene  14% Humulene   6% Linalool  4% β-Pinene   4% α-Pinene 2.5% α-Bisabolol 2.5% Terpineol 2.5% Fenchol2.5% Phytol   1% Nerolidol   1% Geranic acid   1% Camphene   1%Proprietary blend of 7 additional terpenes   3%

Base Composition B was mixed with components in the following amounts toyield the composition of Example 8:

Base Composition B 200 g DMSO (99.995%) 200 ml Gel (70/30 DMSO:Water) 20 g White camphor 1 mL Oil of Wintergreen 5 mL Linalool 1 mL

The composition is a stable lotion that provided fast and effect painrelief when topically applied by several individuals, such as thosereferenced in Examples 11A-11AZ.

Example 9

A liquid pain relief composition was made by combining components in thefollowing amounts:

DMSO 80 mL Glycerin 20 mL Camphor  1 mL CBD 75 mg Klash Terpenes 0.5 mL Water 99 mL

The resulting composition is a stable liquid that provided fast andeffect pain relief when topically applied (e.g., by the 58-year-old manand 54-year-old old ultrarunner).

Example 10

The THC-infused muscle relief lotion of Comparative Example D was mixedwith components in the following amounts to yield the composition ofExample 10:

THC-infused muscle relief lotion 118 ml Base Composition A 159 g DMSO(99.995%) 214 ml Glycerin 53.5 ml  DMSO gel (70%)  42 g Water  21 mlCamphor  2 ml Linalool  2 ml β-Caryophyllene  0.2 ml  Humulene 0.25 ml β-Myrcene  0.5 ml 

The resulting composition was a stable lotion that provided fast andeffect pain relief when topically applied by several individuals, suchas those referenced in Examples 11A-11BA. Some reported even greaterrelief than CBD-only formulations.

Example A

Any of foregoing Examples is modified to include the following terpeneprofile:

Linalool  40% β-Myrcene 20.6%  Limonene 12.7%  β-Caryophyllene 8.1%α-Pinene 6.9% Humulene 3.8% β-Pinene 2.0% α-Bisabolol 1.3% Terpineol1.3% Fenchol 1.3% Phytol 0.5% Nerolidol 0.5% Geranic acid 0.5% Camphene0.5%

When used with several of Examples 7 and also Example 8, the resultingcompositions were highly effective in treating pain.

Example B

Several formulations of Examples 7 and 8 were modified to boost theircannabinoid content. A broad-spectrum CBD oil, which is solid at roomtemperature, was dissolved in DMSO to a concentration of 10% in somecases and 20% in other cases to yield a CBD-infused DMSO concentrate.This solution was added to the compositions to boost the CBD contentprovided by the base lotion composition. By this means, the CBD contentwas increased by 2-10 times. In some formulations, the CBD concentrationwas about 300 mg per fluid ounce. When applied to a region of pain, thecompositions worked well, sometimes better than the originalformulations containing less CBD.

Example C

Several formulations of Examples 7 and 8 were modified to boost andmodify their cannabinoid content. A broad spectrum, hemp-derived delta-8THC oil, which is solid at room temperature, was dissolved in DMSO to aconcentration of 10% to yield a hemp-derived THC-infused DMSOconcentrate. This solution was added to the compositions to add THC toprovide a composition containing both THC and CBD. In some formulations,the THC concentration was about 300 mg per fluid ounce. When applied toa region of pain, these compositions worked well, typically better thanthe original formulations containing only CBD. This suggests thatcombining THC and CBD can provide synergistic pain relief that cannot beobtained using each individually.

Example D

Several formulations of Examples 7 and 8 were modified to boost andmodify their cannabinoid content. The CBD-infused DMSO concentrate ofExample B and the hemp-derived THC infused DMSO concentrate of Example Cwere both added to provide approximately 150 mg of CBD per fluid ounceand approximately 150 mg of THC per fluid ounce, for a total of 300 mgof cannabinoids per fluid ounce. These compositions were perceived towork better than other compositions. Again, this suggests that combiningTHC and CBD provide synergistic pain relief that cannot be obtainedusing each individually.

Examples 11A-11BG (Experimental Uses)

Persons were given one or more compositions of Examples 1-10 andExamples A-D and asked to apply the composition to the affected area.They were instructed to ensure the skin is clean and dry beforeapplication.

Person- Example Age Ailment-Result 11A Woman-36 Chronic hamstring pain;applied to affected area; reduced or eliminated pain 11B Man-48 Golferwith sore forearm; applied to affected area; reduced or eliminated pain11C Man-40 Golfer with sore shoulder that prevented normal swing;applied to affected area; reduced or eliminated pain and restored normalswing 11D Man-50 Tennis elbow; applied to affected are; total relief andrestored normal swing 11E Woman-45 Headache-applied to forehead andobtained total relief 11F Man-58 Painful knee from patellar tendonsurgery (applied to knee; pain reduced from 5 to 1); painful footfollowing ankle surgery (applied to foot; pain reduced from 5 to 0 afterovernight application) 11G Man-54 Runner applied to legs before andafter running; almost total relief 11H Woman-67 Back pain; applied toaffected area; reduced pain from 5 to 1 11I Various Muscle and jointpain; applied to affected areas before and Ultrarunners after runs toprevent and relief pain 11J Man-50 Ultrarunner ran 100 miles, applied toaffected areas after race and next day able to run 20 miles uphill withlittle pain; never recovered so quickly before 11K Man-54 Applied tolegs and feet before running up and down Pfeifferhorn (11,350 ftsummit); felt no pain during hike; when pain later arose applied Example2 over Example 1 for extra relief 11L Man-56 Cancer patient applied tothigh and back; partial relief 11M Woman-27 Massage therapist with sorewrist with cyst; applied to cyst regularly, did not require surgery;cyst pain and size reduced 11N Woman-40 Secretary developed neck painwhile sitting for hours in front of computer; applied to neck; totalpain relief in less than 2 minutes (“I don't know how it works, it justdoes”) 11O Man-32 Sore shoulder; applied to shoulder; pain reduced from5 to 1 within 5 minutes 11P Woman-23 Yoga instructor with pinched nervein back; applied to affected area; obtained almost total relief in <1minute 11Q Man-55 Drummer with chronically sore wrists applied to wristsand ankles and obtained total relief; less effective for back 11R Man-35Soccer goalkeeper applied to sore wrist; total relief 11S Woman-40Massage therapist applied to sore necks of herself and 18- year-olddaughter; both felt pain vanish in minutes 11T Man-60 Has Parkinson’swith painful wrist joints; applied to affected areas; obtained highlevel of relief; uses daily to manage pain 11U Man-37 Hurt back liftingheavy object; hurt two days later and applied to back; relieved the pain11V Woman-41 Wife of man in 11U applied to bursitis and obtained totalrelief 11W Man-58 Recurring pain in thumb from typing at computer-2-3applications to thumb caused pain to subside 11X Man-65 Applied to soreknee after hiking and pain subsided; applied to post-surgical shoulderfor total relief 11Y Man-18 Broken back and laid up for 8 month-appliedto back several times and reduced pain by at least ⅔ 11Z Man-48Chronically painful hands; applied to hand and pain resolved in minutes11AA Man-52 Ultrarunner with back, hip and neck pain previously triedCBD products but obtained no relief; applied composition twice daily andruns virtually pain free; when driving from cabin for 2.5 hours,experienced intense arthritic pain in thumb and index finger, whichlocked up, requiring manual straightening with other hand (see quotebelow); applied product to affected areas and obtained total relief andrestoration of movement 11AB Man-72 Recovered stroke victim with footpain; applied to feet and obtains almost total relief; reducedprescription pain meds by half 11AC Woman-65 Neighbor of man in 11ABapplied to sore thumb and neck and obtained total relief, unlike otherCBD products 11AD Various Friends of Woman in 11AC who drive boatsapplied to hands and arms for instant relief 11AE Man-71 Retired armycolonel has chronic pain and used other CBD products; this compositionworked far better than all others 11AF Man-66 Dentist with chronicshoulder pain almost had to retire; applied to shoulder; productpermitted him to resume working 10-hour days virtually pain-free 11AGWoman-68 Has multiple sclerosis and has sore muscles and joints; triedother CBD products but only this one worked 11AH Man-48 Has chronicarthritis in back and joints and is hunched over much of the time;applied by massage therapist and recovered 90% of normal movement andposture 11AI Man-42 Plantar fasciitis and wakes up hardly able to walk;applied to bottom of feet each night before bed and woke up pain free;after 6 months pain permanently went away 11AJ Woman-67 Plantarfasciitis; applied to feet; obtained almost total relief 11AK Man-45Very painful and stiff shoulders; applied to shoulders by massagetherapist and recovered range of motion 11AL Man-84 Age-related pain;applied to affected areas to effectively relieve pain 11AM Woman-87 Soreneck; applied to neck as needed for high level of relief 11AN Woman-30Professional skier with muscular and joint pain; applied to affectedareas for high level of relief 11AO Woman-62 Receptionist with chronicpain in thumb joint; provided total relief when applied to jointregularly; stopped using for 3 weeks and pain returned; next applicationrelieved pain as before 11AP Woman-30 Effective for direct applicationto affected area to treat recurring back pain 11AQ Man-81 Walks with acane; applied to affected areas; effective for back pain, leg pain,ankle, foot pain, and arthritic pain 11AR Man-48 Elbow Pain from celiacdisease; applied to affected area; provided 80-90% reduction in pain11AS Man-50 Recovering from deltoid muscle surgery-applied to deltoid tomanage pain post-surgery (60-80% reduction in pain) 11AT Man-55Developed painful sciatica and could barely walk; applied to buttocksand back and was able to hike 8 miles 11AU Woman-84 Had a locked fingerand sore neck; applied to neck using hand and said it didn’t providetotal relief; inadvertently unlocked finger of applying hand 11AV Man-43Same man in 11AI had intense shoulder pain under the scapula; applied toaffected area and obtained total relief 11AW Man-58 Building contractorhad hands so painful he could no longer hold tools and was going toquit; applies to hands daily to obtain relief sufficient to continueworking with little to no pain. 11AX Man-60 Same man in 11F had sore ITband a few days after strenuous hike; applied one time to affected areaalong outside of thigh before bed; pain completely gone next day 11AYMan-45 Had sore forearms from heavy lifting during home remodel; appliedproduct to affected areas; obtained almost total relief 11AZ Woman-47Pain in tendon connecting thigh to pelvis following workouts; applied toaffected area; provided total relief after 2 applications 11BA Man-41Body builder suffering from inner tendonitis at the elbow where thebicep muscle attaches to the ulna regularly applied to affected area torelieve pain and promote healing during physical therapy; cancelledsurgery 11BB Man-70 “I've battled fibromyalgia, degenerate disc, bonespurs, old back fractures, arthritis, now a broken leg 2 months ago.I've [sic] very used to physical pain daily. It absolutely still blowsmy mind how well this works!” 11BC Man-60 The inventor obtainedpermanent relief for intense neck- trapezius-shoulder pain after just afew days of application; first application reduced pain from 7 to 0within minutes; applies about once a month for maintenance if neckstiffens for total relief. 11BD Man-38 Had sciatica; applied to lowerback and pain eliminated. 11BE Man-35 Had sciatica; applied to lowerback and pain eliminated. 11BF Man-30 Overweight man with back pain;very effective to eliminate pain when needed. 11BG Man-40 “Salveation isinstant relief when I've hurt my back. I also use it preemptively if Iknow I am going to be doing an activity that is going to strain my back.I use it primarily on my lower back on the area around my L1 & L2 discs,as they both have degeneration issues. The salve will take me from a 7(on a scale of 1-10, 10 the worst) down to a 3 in short order. I gladlyendorse the salve to anyone who has moderate to severe back pain.”

Ultrarunner in Example 11AA wrote the following: “I didn't want to soundover the top in the last review I sent you but I need to tell you theother two things that Salvation has done for me: (1) I have badarthritis in my thumb and index finger on my left hand. Yesterday whiledriving home from our cabin they would lock up in a half first positionand I would have to straighten them back out with my other hand. Thishappened at least a dozen times in the 2½ hour drive. As soon as I gothome, I put Salvation on them and the pain and cramps went away. I'msure they will return in the future but now I have a remedy. (2) I havesuffered with plantar fasciitis for over 30 years. Two surgeries andseveral shots later there was no hope. I started running when I was 46and that and 0 drop Altras seemed to be my cure. Due to my neck issues Iquit running for six months and now the PF has returned with avengeance. I work 10 hour days in steel toe boots standing on concreteand by the end of my shift I could hardly walk. I started pre treatingwith Salvation and I am mostly pain free. This stuff really has been mySalvation!”

The disclosed compositions have been found to be especially useful intreating chronic pain, including idiopathic pain with no specificpathology or known cause, and in older (e.g., 50 or above) or infirmpersons, who have tried conventional pain remedies with little or norelief. The product has been described as miraculous by many. Because itdoes not feel like a counterirritant, it does not provide the usualcooling and/or heating sensation of such products. Rather, it seems towork to reduce or eliminate pain through a different mechanism. Somehave proclaimed “it just works”.

Comparative Study

A comparative study was performed comparing a preferred composition madeaccording with a representative composition in US Publication No.2016/0256411 (Aung-Din), which discloses a method of administering acannabinoid to the back of the neck region at the hairline (BONATH) inorder to deliver the cannabinoid to the brain stem and/or trigeminalnerves to provide pain relief to a different part or region of the body.This is called topical regional neuro-affective therapy (“TRNAtherapy”).

Example 3 of Aung-Din is the only working example of a composition whichcontains DMSO and CBD and is therefore a valid representativecomposition of Aung-Din. Following is a quotation of Example 3:

Example 3 Oil-Based CBD

A 30 g topical formulation of CBD is prepared by incorporating CBD oil,Dimethyl sulfoxide 3 ml and enough base for total quantity of 30 grams.The CBD is incorporated in a concentration sufficient to yield an endproduct having a CBD concentration of 0.75%, 1%, 1.5%, 2% and 3%. Thetopical formulation is in the form of a cream. The oil-based CBDincludes CBD oil commercially available from CannaVest. A unit dose ofthe topical CBD cream is from about 0.5 to about 1 g, with respect toformulations having a CBD concentration from 1.5%-3%. After initialapplication, the topical CBD formulation can be applied to the back ofthe neck of the human patient once a day, twice a day, three times aday, or four times a day depending on the condition to be treated andits severity.

Example 3 therefore provides the following information about thecomposition:

-   -   3 ml of DMSO;    -   CBD oil incorporated in a concentration sufficient to yield an        end product having a CBD concentration of 0.75%, 1%, 1.5%, 2%,        or 3% CBD; and    -   enough base for a total of 30 grams of topical formulation.

Aung-Din does not identify what is in the “base” used in Example 3.Paragraph [0180] of Aung-Din is the only place where a definition of a“base” is provided: “Carrier materials suitable for use in the instantcompositions include those well-known for use in the cosmetic andmedical arts as bases for ointments, lotions, salves, aerosols,suppositories and the like.” Thus, ointments, lotions, and salves usedin the cosmetic and medical arts are all suitable “bases” forreproducing Example 3 of Aung-Din.

The CBD lotion or cream identified as “Base Composition A” and used inExamples 7A-7R above was determined to a suitable “base”. It is soldcommercially by Koodegras (CBD store), located in Salt Lake City, Utah.A gallon of Base Composition A was purchased directly from themanufacturer and used to make the compositions for the ComparativeStudy.

As set forth above, Base Composition A contained the followingcomponents:

  Purified water Capric/Caprillic Triglycerides Sunflower Seed Oil HempCBD Oil with Terpenes Moroccan Organic Argan Oil Emulsifying WaxGlyceryl Monostearate Simmondsia (jojoba) oil Butyrospermum Parkii (SheaButter) Stearic Acid Cetyl Alcohol Glyceryl Distearate Carbomer.

Base Composition A contained 10,000 mg of CBD per gallon (0.26% byweight) and terpenes, which are identified in paragraph [0105] of theApplication as being linalool (75%), α-pinene (11%), β-myrcene (10.5%),β-caryophyllene (2%), and humulene (1.5%). The weight ratio of CBD wasabout 3 parts CBD to about 1 to 2 parts of total terpenes.

A composition representative of Example 3 of Aung-Din (“Aung-DinComposition”) was made by mixing CBD oil, DMSO, and Base Composition Ain the same relative amounts set forth in paragraph [0220] of Aung-Dinto yield a composition containing 1.5% by weight of CBD:

CBD Oil q.s to 1.5 wt % DMSO 30 ml Base Composition A q.s. to 300 g

A representative composition of the disclosure (“Inventive composition”)was made by mixing together the following components to yield acomposition containing CBD and other hemp-derived cannabinoids totaling0.75% by weight:

Base Composition A  932 g DMSO  932 g Glycerin 37.3 g Water 93.2 gAqueous gel (2% carbomer)   90 g CBD and hemp-derived cannabinoids 13.5g Terpenes   7 g Total 2,105 g 

The Aung-Din Composition contained approximately twice the concentrationof CBD as the combined concentration of CBD and other hemp-derivedcannabinoids in the Inventive Composition and approximately one-fourththe concentration of DMSO.

The participants of the comparative study were provided with quantitiesof the Aung-Din Composition and the Inventive Composition and asked todefine their pain on a scale of 1 to 10 before and 15-30 minutes afterusing each composition. The recommended amount to be applied was anickel-sized amount.

An 83 year old man suffering from intense chronic lower back pain, withan initial pain level of 10, applied the Inventive Composition to thelower back at the location of the pain and obtained a high level ofrelief, reducing the pain level from 10 to 2. When the pain returned,the man applied the Aung-Din Composition to the lower back and obtainedno discernable relief. Thereafter, the man applied the InventiveComposition to the lower back at the location of the pain when the painlevel was 9 and again obtained a high level of relief, reducing the painlevel from 9 to 1.

A 55 year old woman suffering from intense neck pain from working longhours typing at a computer, with an initial pain level of 8, applied theInventive Composition to the neck at the location of the pain andobtained a high level of relief, reducing the pain level from 8 to 2.When the pain returned, the woman applied the Aung-Din Composition tothe neck and obtained no discernable relief (initial and final painlevels were 8). Thereafter, the woman applied the Inventive Compositionto the neck at the location of the pain when the pain level was 8 andagain obtained a high level of relief, reducing the pain level from 8 to2.

A 30 year old man suffering from periodic lower back pain, with aninitial pain level of 5, applied the Inventive Composition to the lowerback at the location of the pain and obtained significant pain relief,reducing the pain level from 5 to 2. When the pain returned, the manapplied the Aung-Din Composition to the lower back, which only slightlyreduced the pain level from 5 to 4. Thereafter, the man applied theInventive Composition to the lower back at the location of the pain whenthe pain level was 5 and again obtained significant pain relief,reducing the pain level from 5 to 2.

A 49 year old man suffering from celiac disease commonly experiencespain in the elbow and fingers. When the pain was at an initial painlevel of 5, the man applied the Inventive Composition at the location ofthe pain and obtained total relief, with a pain level of 0. When thepain returned, the man applied the Aung-Din Composition at the locationof the pain and obtained no discernable relief (initial and final painlevels were 5). Thereafter, the man applied the Inventive Composition atthe location of the pain when the pain level was 5 and again obtained ahigh level of relief, reducing the pain level from 5 to 1.

A 57 year old man suffering from pain in the wrists, hands and feet,with an initial pain level of 7, applied the Inventive Composition atthe location of the pain and obtained significant relief, with aresulting pain level of 4. When the pain returned, the man applied theAung-Din Composition at the location of the pain, which only slightlyreduced the pain level from 7 to 6. Thereafter, the man applied theInventive Composition at the location of the pain when the pain levelwas 6 and again obtained a high level of relief, reducing the pain levelfrom 6 to 2.

A 49 year old man suffering from pain in the thumb joints of both hands,with an initial pain level of 6, applied the Inventive Composition atthe location of the pain and obtained total relief, reducing the painlevel from 6 to 0. When the pain returned to a pain level of 5, the manapplied the Aung-Din Composition at the location of the pain andobtained no discernable relief (beginning and final pain levels were 5).Thereafter, the man applied the Inventive Composition at the location ofthe pain when the pain level was 5 and again obtained total relief,reducing the pain level from 5 to 0.

A 60 year old man suffering from neck, knee, and foot pain of varyingdegrees, applied the Inventive Composition to the neck and obtainedalmost total relief, reducing the pain level from 7 to 1. When the painreturned to a pain level of 4, the man applied the Aung-Din Compositionto the location of the pain and obtained no discernable relief(beginning and final pain levels were 4). Thereafter, the man appliedthe Inventive Composition to the neck when the pain level was 5 andagain obtained total relief, reducing the pain level from 5 to 0.

The 60 year old man applied the Inventive Composition to a footexperiencing neuropathic pain at a pain level of 5 and obtained almosttotal relief to a pain level of 1 after overnight application. A similarovernight application of the Aung-Din Composition to the same foot whenthe neuropathic pain returned to a pain level of 4 resulted in nodiscernable relief. The man routinely applies the Inventive Compositionto the foot when sore and obtains a high level of relief.

A 49 year old woman who recently had neck surgery, with an initial painlevel of 8, applied the Inventive Composition to the neck and obtainmodest pain reduction to a pain level of 5 or 6. When the pain returnedto a pain level of 8, the woman applied the Aung-Din Composition at thelocation of the pain and was only able to reduce the pain level from 8to 7. Thereafter, the woman applied the Inventive Composition at thelocation of the pain when the pain level was 8 and obtained modestrelief down to a pain level of 6.

A 43 year old man who had recently competed in an ultramarathon hadlower back pain at an initial pain level of 4. The Aung-Din Compositionwas applied at the location of the pain and provided a modest amount ofrelief from 4 to 3. Thereafter, when the pain returned to a pain levelof 4, the Inventive Composition was applied at the location of the painand reduced the pain from a pain level of 4 to 1.

A 29 year woman suffering from pain in the wrists, lower back, and neckwith an initial pain level of 9, applied the Inventive Composition atthe location of the pain and obtained significant relief, reducing thepain level from 9 to 3. When the pain returned to a pain level of 9, thewoman applied the Aung-Din Composition at the same location and obtainedslight relief from 9 to 7. Thereafter, the woman applied the InventiveComposition at the location of the pain when the pain level was 9 andagain experienced significant relief from a pain level of 9 to 4.

A 52 year woman suffering from pain in the neck, mid back, and kneeswith an initial pain level of 4, applied the Inventive Composition atthe location of the pain and obtained total relief, reducing the painlevel from 4 to 0. When the pain returned to a pain level of 3, thewoman applied the Aung-Din Composition at the same location and obtainedno discernable relief. Thereafter, the woman applied the InventiveComposition at the location of the pain when the pain level was 4 andagain experienced total relief from a pain level of 4 to 0.

The Comparative Study shows that the Inventive Composition wassignificantly more effective than the Aung-Din Composition in providinglocalized pain relief, i.e., at the location where applied.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

1. A composition for topical pain relief, comprising: a cannabinoidcomponent; 15% to 75% by weight of dimethyl sulfoxide (DMSO); water; afatty component; and a compatibilizer, wherein the composition containsgreater than 35% by combined weight of the DMSO, water, andcompatibilizer.
 2. The composition of claim 1, further comprising aterpenoid component selected from the group consisting of α-pinene,β-pinene, camphene, β-myrcene, humulene, α-bisabolol, β-caryophyllene,linalool, camphor, limonene, ocimene, α-phellandrene, 1,8-ceneole,eucalyptol, γ-terpinene, terpineol, fenchol, phytol, nerolidol, geranylacetate, sabinene, p-cymene, β-phellandrene, valencene, borneol,isoborneol, geraniol, δ-3-carene, terpinolene, and combinations thereon.3. The composition of claim 2, wherein the ratio (w/w) of totalterpenoids to total cannabinoids is in a range of about 1:10 to about5:1;
 4. The composition of claim 2, wherein the cannabinoid componentcomprises at least one of cannabidiol (CBD) or tetrahydrocannabinol(THC) and the terpenoid component comprises at least three of linalool,α-pinene, β-myrcene, β-caryophyllene, or humulene and/or at least fiveof β-myrcene, limonene, β-caryophyllene, humulene, linalool, β-pinene,α-pinene, α-bisabolol, terpineol, fenchol, phytol, nerolidol, geranylacetate, or camphene.
 5. The composition of claim 1, wherein thecannabinoid component is selected from the group consisting ofcannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN),cannabigerol (CBG), cannabichchromene (CBC), cannabicyclol (CBL),tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin(CBCV), cannabigerovarin (CBGV), delta-8-tetrahydrocannabinol,delta-9-tetrahydrocannabinol (Dronabinol), cannabigerol monomethyl ether(CBGM), nabilone, and combinations thereof.
 6. The composition of claim1, wherein the composition comprises about 20% to about 70% by weight ofthe DMSO.
 7. The composition of claim 1, wherein the compatibilizer isselected from the group consisting of alcohols, polyols, thiols,carboxylic acids, carboxylates, polycarboxylates, esters, amides,ketones, aldehydes, ethers, sulfonates, phosphonates, and amines.
 8. Thecomposition of claim 7, wherein the compatibilizer comprises one or morepolyols selected from the group consisting of glycerin, propyleneglycol, 1,3-propanediol, 1,3-butanediol, sorbitol, xylitol, andpolyethylene glycol.
 9. The composition of claim 1, wherein the fattycomponent comprises one or more components selected from the groupconsisting of fatty acids, caproic acid, capric acid, caprillic acid,lauric acid, medium chain fatty acids, stearic acid, isostearic acid,octanoic acid, oleic acid, linoleic acid, linolenic acid, esters offatty acids, mono-, di- and/or triglycerides of fatty acids, olive oil,sunflower seed oil, coconut oil, cocoa butter, jojoba oil, almond oil,pine needle oil, shea butter, argan oil, nigella sativa oil, beeswax,and flaxseed oil.
 10. The composition of claim 1, wherein thecomposition is an emulsion.
 11. The composition of claim 1, wherein thecomposition is a cream, lotion, gel, suspension, ointment, or liquid.12. A kit comprising the composition of claim 1 in a container and aplurality of bandages, patches, or other barrier layers.
 13. An articleof manufacture comprising the composition of claim 1 and a bandage,patch, or other barrier layer on which the composition is disposed. 14.A composition for topical pain relief, comprising: 0.05-10% by weight ofat least one cannabinoid; 0.002% to about 4% by weight of a plurality ofat least one terpenoid; 20% to 80% by weight of DMSO; a compatibilizer;water; and a fatty component, wherein the composition is an emulsion,wherein the composition contains greater than 35% by combined weight ofthe DMSO, compatibilizer, and water.
 15. The composition of claim 14,wherein the at least one cannabinoid comprises CBD and THC.
 16. Thecomposition of claim 15, wherein the terpenoid component comprises atleast two of linalool, α-pinene, β-myrcene, β-caryophyllene, orhumulene.
 17. The composition of claim 15, wherein the THC comprisesdelta-8 THC.
 18. A composition for targeted topical pain relief,comprising: 0.05% to 10% by combined weight of at least one cannabinoidselected from the group consisting of cannabidiol (CBD),tetrahydrocannabinol (THC), and optionally one or more oftetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA),cannabinol (CBN), cannabigerol (CBG), cannabichchromene (CBC),tetrahydrocannabivarin (THCV), cannabicyclol (CBL), cannabidivarin(CBDV), cannabichromevarin (CBCV), and cannabigerovarin (CBGV); 0.002%to about 4% by combined weight of at least one terpenoid selected fromthe group consisting of α-pinene, β-pinene, camphene, β-myrcene,humulene, α-bisabolol, β-caryophyllene, linalool, camphor, limonene,ocimene, α-phellandrene, 1,8-ceneole, eucalyptol, γ-terpinene,terpineol, fenchol, phytol, nerolidol, geranyl acetate, sabinene,p-cymene, β-phellandrene, valencene, borneol, isoborneol, geraniol,δ-3-carene, and terpinolene, wherein the ratio (w/w) of total terpenoidsto total cannabinoids is in a range of about 1:5 to about 2:1; 25% to70% by weight of dimethyl sulfoxide (DMSO); water; a fatty component;and a compatibilizer.
 19. The composition of claim 18, wherein thecomposition contains only hemp-derived cannabinoids.
 20. The compositionof claim 18, wherein: the compatibilizer is selected from the groupconsisting of alcohols, polyols, thiols, carboxylic acids, carboxylates,polycarboxylates, esters, amides, ketones, aldehydes, ethers,sulfonates, phosphonates, and amines, the fatty component is selectedfrom the group consisting of fatty acids, caproic acid, capric acid,caprylic acid, lauric acid, medium chain fatty acid, stearic acid,isostearic acid, octanoic acid, oleic acid, linoleic acid, linolenicacid, esters of fatty acids, mono-, di- and/or triglycerides of fattyacids, olive oil, sunflower seed oil, coconut oil, cocoa butter, jojobaoil, almond oil, pine needle oil, shea butter, argan oil, nigella sativaoil, beeswax, and flaxseed oil, and the composition is a cream, lotion,gel, suspension, ointment, or liquid.